1. Field of the Invention
The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of Cathepsin S.
2. Background
Cysteine proteases represent an enzymatic class of proteins that catalyze the hydrolysis of peptide bonds by a nucleophilic sulfhydryl group of a cysteine residue in the active site of the enzyme. Cathepsins are a subclass of cysteine protease that play a major role in lysosomal, endosomal, and extracellular protein degradation and have thus been implicated in many disease processes. Cathepsin S [EC 3.4.22.27] has been shown to be required for proper MHC class II antigen presentation. As a result of its non-redundant role in MHC class II antigen presentation, cathepsin S has been associated with several normal and disease processes in mammals. These diseases or disorders include, but are not limited to: osteoporosis, osteoarthritis, muscular dystrophy, inflammation, tumor invasion, glomerulonephritis, malaria, periodontal disease, metachromatic leukodystrophy, periodontal diseases, Paget's disease, atherosclerosis, multiple sclerosis, rheumatoid arthritis, juvenile onset diabetes, lupus, asthma, tissue rejection, Alzheimer's disease, Parkinson's disease, neuronal degeneration, shock, cancer, malaria, neuropathic pain, COPD, inflammatory bowel disease, allergy, Chagas, leishmaniasis, shistosomiasis, and African trypanosomiasis.
The novel compounds of this invention inhibit the activity of cathepsin S and are, therefore, expected to be useful in the treatment of cathepsin S-associated diseases.